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IntroductionMorroniside (Mor) is a bioactive compound found in Corni Fructus (CF) [Cornaceae; Cornus officinalis Siebold & Zucc.], which has been used as medicine and food in China, Korea, and Japan for over 2,000 years. This review summarizes recent progress on Mor, specifically focusing on its distribution, isolation, detection, and various pharmacological effects.MethodsA literature survey on Mor was conducted using electronic databases such as PubMed, ScienceDirect, CNKI, and Google Scholar. After removing TCM prescription-related standards, medicinal herb processing-related research, and other irrelevant works of literature, we obtained relevant information on Mor’s biological and pharmacological properties.ResultsThe main conclusions are as follows: Mor is widely distributed in the plant kingdom; the methods for extracting and isolating Mor are well established; and the technology for detecting it is accurate. Mor exhibits numerous pharmacological effects. Along with CF, Mor has shown renoprotective effects against diabetes, hepatoprotective effects against diabetes, triptolide, and nonalcoholic steatohepatitis, and boneprotective effects against osteoporosis and osteoarthritis. In addition, researchers have also explored other pharmacological effects of Mor, including neuroprotective effects against focal cerebral ischemia, spinal cord injury, and Alzheimer’s disease; cardioprotective effects against acute myocardial infarction; protection of the digestive system from gastritis, inflammatory bowel disease, and colitis; protection of the skin by promoting hair growth, wound healing, and flap survival; and protection of the lungs from acute lung injury and pulmonary fibrosis. Moreover, Mor has anti-obesity effects, anti-inflammatory effects in the eye, and improves follicular development.DiscussionOverall, this review provides a comprehensive understanding of the pharmacological effects of Mor, from which the limitations of the current research can be understood, which will help facilitate future research.

Existing visual simultaneous localization and mapping (V-SLAM) algorithms are usually sensitive to the situation with sparse landmarks in the environment and large view transformation of camera motion, and they are liable to generate large pose errors that lead to track failures due to the decrease of the matching rate of feature points. Aiming at the above problems, this article proposes an improved V-SLAM method based on scene segmentation and incremental optimization strategy. In the front end, this article proposes a scene segmentation algorithm considering camera motion direction and angle. By segmenting the trajectory and adding camera motion direction to the tracking thread, an effective prediction model of camera motion in the scene with sparse landmarks and large view transformation is realized. In the back end, this article proposes an incremental optimization method combining segmentation information and an optimization method for tracking prediction model. By incrementally adding the state parameters and reusing the computed results, high-precision results of the camera trajectory and feature points are obtained with satisfactory computing speed. The performance of our algorithm is evaluated by two well-known datasets: TUM RGB-D and NYUDv2 RGB-D. The experimental results demonstrate that our method improves the computational efficiency by 10.2% compared with state-of-the-art V-SLAMs on the desktop platform and by 22.4% on the embedded platform, respectively. Meanwhile, the robustness of our method is better than that of ORB-SLAM2 on the TUM RGB-D dataset.

NK cells play crucial roles in defending against persistent HBV. However, NK cells present dysfunction in chronic hepatitis B virus (CHB) infection, and the associated mechanism is still not fully understood. Except for the regulatory receptors, NK cells could also be regulated by the surface and intracellular pattern recognition receptors (PRRs). In the present study, we found that the level of the adaptor of DNA sensor STING in NK cells was significantly decreased in HBeAg-negative CHB patients, and it was positively associated with the degranulation ability of NK cells. Compared to NK cells from healthy donors, NK cells from HBeAg-negative CHB patients displayed a lower responsiveness to cGAMP stimulation. Further investigation showed that HBsAg could inhibit the STING expression in NK cells and suppress the response of NK cells to cGAMP. Significantly, STAT3 was identified to be a transcription factor that directly regulated STING transcription by binding to the promoter. In addition, STAT3 positively regulated the STING associated IFN-α response of NK cells. These findings suggested that STING is an important adaptor in NK cell recognition and activation, while HBsAg disturbs NK cell function by the STAT3-STING axis, providing a new mechanism of NK disability in HBeAg-negative CHB infection.

Emerging evidence indicates that cancer cell-derived exosomes contribute to cancer progression through the modulation of tumor microenvironment, but the underlying mechanisms are not fully elucidated. Here, we reported that hepatocellular carcinoma (HCC)-derived exosomes could remodel macrophages by activating NF-κB signaling and inducing pro-inflammatory factors, and resulted in M2-polarized tumor-associated macrophages. In addition, the expression of IFN-γ and TNF-α was inhibited, while the expression of inhibitory receptors such as PD-1 and CTLA-4 was upregulated in T cells by HCC-derived exosome educated macrophages. Data also revealed that HCC exosomes were enriched with miR-146a-5p and promoted M2-polarization. Further investigation demonstrated that the transcription factor Sal-like protein-4 (SALL4) was critical for regulating miR-146a-5p in HCC exosomes and M2-polarization. Mechanistically, SALL4 could bind to the promoter of miR-146a-5p, and directly controlled its expression in exosomes. Blocking the SALL4/miR-146a-5p interaction in HCC reduced the expression of inhibitory receptors on T cells, reversed T cell exhaustion, and delayed HCC progression in DEN/CCL4-induced HCC mice. In conclusion, identification of a role of the exosomal SALL4/miR-146a-5p regulatory axis in M2-polarization as well as HCC progression provides potential targets for therapeutic and diagnostic applications in liver cancer.

TLR2 signaling plays a critical protective role against acute Listeria monocytogenes (Lm) infection by up-regulating inflammatory cytokines and promoting macrophage antimicrobial capabilities. However, the underlying mechanism by which TLR2 regulates hepatic macrophage-mediated anti-Lm immune responses remains poorly understood. In this study, we found that both the absolute number and proportion of monocyte/macrophage (Mo/MΦ) in the liver and spleen of Tlr2−/− mice were significantly lower compared to wild type mice. Changes in TLR2 signaling in both hepatocytes and Mo/MΦs were associated with the infiltration of Mo/MΦs in response to Lm-infection. Analyses by proteome profiler array and ELISA revealed that hepatocytes recruited Mo/MΦs via TLR2-dependent secretion of CCL2 and CXCL1, which was confirmed by receptor blocking and exogenous chemokine administration. Importantly, we found that TLR2 contributed to macrophage mobility in the liver through a TLR2/NO/F-actin pathway, facilitating the formation of macrophage-associated hepatic microabscesses. Moreover, TLR2 activation induced the expression of several PRRs on hepatic macrophages associated with the recognition of Lm and augmented macrophage bacterial clearance activity. Our findings provide insight into the intrinsic mechanisms of TLR2-induced Mo/MΦ migration and mobility, as well as the interaction between macrophages and hepatocytes in resistance to Lm infection.

Background. Overfishing and habitat degradation caused a decline of populations of many fish species belonging to the speciose family Sciaenidae. A reliable taxonomic framework is a prerequisite for implementing effective stock management and conservation measures, but phylogeny and taxonomy of the Sciaenidae remain poorly resolved. As traditionally used morphological and single gene-based molecular markers carry a too limited phylogenetic signal for the task, mitochondrial phylogenomics may be a more suitable tool. The freshwater drum, Aplodinotus grunniens Rafinesque, 1819, is one of the few Sciaenidae species that live in freshwater habitats, which makes it an important model for studying the phylogeny and evolution of Sciaenidae. Material and methods. We sequenced and characterized its mitogenome, and reconstructed the phylogeny of Sciaenidae using mitogenomes of 28 species. Results. The architecture of the mitogenome (16487 bp in length) is standard for this family, and three typical elements were identified in the control region: extended termination associated sequences, central conserved region, and conserved sequence block. Poor availability of sciaenid mitogenomes (especially those belonging to different lineages) prevented us from resolving the phylogeny of this family with confidence. Notably, our results indicate that Larimichthys and Collichthys species may belong to a single genus, and we suspect that the mitogenome of Chrysochir aureus (Richardson, 1846) has been misidentified taxonomically, and urge its resequencing. Conclusion. The sequencing of additional mitogenomes belonging to non-represented and poorly represented lineages is needed to facilitate the understanding of phylogeny and taxonomy of Sciaenidae. [ABSTRACT FROM AUTHOR]

Inflammation is a major contributing factor in the development of diabetic microvascular complications, regardless of whether improved glycaemic control is achieved. Studies have increasingly indicated that fenofibrate, a lipid-lowering therapeutic agent in clinical use, exerts a potential anti-inflammatory effect, which is mediated by sirtuin 1 (SIRT1; an NAD+-dependent deacetylase) in endothelial cells. The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR). The data demonstrated that high glucose treatment in human retinal endothelial cells (HRECs) inhibited the expression and deacetylase activity of SIRT1. The reduction of SIRT1 expression and deacetylase activity persisted following a return to normal glucose levels. Furthermore, nuclear factor-B expression was observed to be negatively correlated with SIRT1 expression and activity in HRECs under high glucose levels and the subsequent return to normal glucose levels. Fenofibrate treatment abrogated these changes. Knockdown of SIRT1 attenuated the effect of fenofibrate on high glucose-induced NF-B expression. In addition, fenofibrate upregulated SIRT1 expression through peroxisome proliferator-activated receptor a in high glucose-induced metabolic memory. These findings indicate that fenofibrate is important in anti-inflammatory processes and suppresses the cellular metabolic memory of high glucose-induced stress via the SIRT1-dependent signalling pathway. Thus, treatment with fenofibrate may offer a promising therapeutic strategy for halting the development of DR and other complications of diabetes. [ABSTRACT FROM AUTHOR]

Cellular metabolic memory occurs in diabetic microvascular and macrovascular complications, but the underlying mechanisms remain unclear. Here, we investigate the role of sirtuin 1 (SIRT1) and metformin in this phenomenon. In bovine retinal capillary endothelial cells (BRECs) and retinas of diabetic rats, the inflammatory gene, nuclear factor-ĸB(NF-ĸB), and the proapoptotic gene, Bax, induced by hyperglycemia, remained elevated after returning to normoglycemia. BRECs with small interfering RNA--mediated SIRT1 knockdown had increased sensitivity to hyperglycemia stress, whereas SIRT1 overexpression or activation by metformin inhibited the increase of mitochondrial reactive oxygen species--mediated glyceraldehyde-3-phosphate dehydrogenase by poly (ADP-ribose) polymerase (PARP) activity through the upregulation of liver kinase B1/AMP-activated protein kinase (LKB1/AMPK), ultimately suppressing NF-ĸB and Bax expression. Furthermore, we showed that hyperglycemia led to PARP activation, which in turn may have downregulated SIRT1. Of importance, this study also demonstrated that metformin suppressed the "memory" of hyperglycemia stress in the diabetic retinas, which may be involved in the SIRT1/LKB1/AMPK pathway. Our data suggest that SIRT1 is a potential therapeutic target for the treatment of the cellular metabolic memory, and the use of metformin specifically for such therapy may be a new avenue of investigation in the diabetes field. Diabetes 61:217--228, 2012 [ABSTRACT FROM AUTHOR]

OBJECTIVE--Mitochondrial reactive oxygen species (ROS) plays a key role in diabetic retinopathy (DR) pathogenesis. However, whether simvastatin decreases diabetes-induced mitochondrial ROS production remains uncertain. The aim of this study was to clarify the beneficial effects and mechanism of action of simvastatin against diabetes-induced retinal vascular damage. RESEARCH DESIGN AND METHODS--Diabetic rats and control animals were randomly assigned to receive simvastatin or vehicle for 24 weeks, and bovine retinal capillary endothelial cells (BRECs) were incubated with normal or high glucose with or without simvastatin. Vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in the rat retinas or BRECs were examined by Western blotting and real-time RT-PCR, and poly (ADPribose) polymerase (PARP), and p38 MAPK were examined by Western blotting. Mitochondrial membrane potential (δψm) and ROS production were assayed using the potentiometric dye 5,5',6,6'- Tetrachloro 1, l',3,3'-tetraethyl-benzimidazolylcarbocyanine iodide (JC-1) or CM-H2DCFDA fluorescent probes. RESULTS--Simvastatin significantly upregulated PGC-1α (P < 0.01), subsequently decreased δψm (P < 0.05) and ROS generation (P < 0.01), inhibited PARP activation (P < 0.01), and further reduced VEGF expression (P < 0.01) and p38 MAPK activity (P < 0.01). Those changes were associated with the decrease of retinal vascular permeability, retinal capillary cells apoptosis, and formation of acellular capillaries. CONCLUSIONS--Simvastatin decreases diabetes-induced mitochondrial ROS production and exerts protective effects against early retinal vascular damage in diabetic rats in association with the inhibition of mitochondrial ROS/PARP pathway mediated by PGC-1α. The understanding of the mechanisms of action of statins has important implications in the prevention and treatment of mitochondrial oxidative stress-related illness such as DR. Diabetes 59:2315-2325, 2010 [ABSTRACT FROM AUTHOR]